Featured Publications
Single-cell epigenetic, transcriptional, and protein profiling of latent and active HIV-1 reservoir revealed that IKZF3 promotes HIV-1 persistence
Wei Y, Davenport T, Collora J, Ma H, Pinto-Santini D, Lama J, Alfaro R, Duerr A, Ho Y. Single-cell epigenetic, transcriptional, and protein profiling of latent and active HIV-1 reservoir revealed that IKZF3 promotes HIV-1 persistence. Immunity 2023, 56: 2584-2601.e7. PMID: 37922905, PMCID: PMC10843106, DOI: 10.1016/j.immuni.2023.10.002.Peer-Reviewed Original ResearchConceptsTranscription factor accessibilityHIV-1-infected cellsFactor accessibilityHIV-1 persistenceHeterogeneous cellular statesEpigenetic programsCellular programsCellular statesLatent HIV-1-infected cellsProliferation programProtein profilingSuppressive antiretroviral therapyHIV-1 eradicationHIV-1 reservoirCell deathProtein statesHIV-1 RNAAP-1HIV-1 DNASurface proteinsMechanistic interrogationEpigeneticsAntiretroviral therapyMemory CD4Effector differentiationSingle-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones
Collora JA, Liu R, Pinto-Santini D, Ravindra N, Ganoza C, Lama JR, Alfaro R, Chiarella J, Spudich S, Mounzer K, Tebas P, Montaner LJ, van Dijk D, Duerr A, Ho YC. Single-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones. Immunity 2022, 55: 1013-1031.e7. PMID: 35320704, PMCID: PMC9203927, DOI: 10.1016/j.immuni.2022.03.004.Peer-Reviewed Original ResearchConceptsHIV-1 eradicationHIV-1 RNAHIV-1Effector memory Th1 cellsHIV-1-infected individualsHIV-1-infected CD4Clonal expansionCell clonesMemory Th1 cellsCell clonal expansionPersistent antigenAntiretroviral therapyViral suppressionCytotoxic CD4Cytotoxic TTh1 cellsAntigen stimulationClonal expansion dynamicsUninfected individualsSurface protein expressionTNF responseUnstimulated conditionsTCR sequencesProtein expressionCD4Inhibition of a Chromatin and Transcription Modulator, SLTM, Increases HIV-1 Reactivation Identified by a CRISPR Inhibition Screen
Pedersen SF, Collora JA, Kim RN, Yang K, Razmi A, Catalano AA, Yeh YJ, Mounzer K, Tebas P, Montaner LJ, Ho YC. Inhibition of a Chromatin and Transcription Modulator, SLTM, Increases HIV-1 Reactivation Identified by a CRISPR Inhibition Screen. Journal Of Virology 2022, 96: e00577-22. PMID: 35730977, PMCID: PMC9278143, DOI: 10.1128/jvi.00577-22.Peer-Reviewed Original ResearchConceptsHIV-1-infected cellsHIV-1 reactivationT cell clonesHIV-1HIV-1 protein expressionAntiretroviral therapyDrug treatmentProtein expressionInfected cellsInfected individualsHIV-1-infected individualsCell clonesEffective antiretroviral therapyHIV-1 cureLong-term therapyHIV-1 gene expressionHIV-1 persistenceHIV-1 provirusHIV-1 transcriptionImmune cell killingNovel therapeutic targetCell deathLatent reservoirImmune cellsT cellsFilgotinib suppresses HIV-1-driven gene transcription by inhibiting HIV-1 splicing and T cell activation
Yeh YJ, Jenike KM, Calvi RM, Chiarella J, Hoh R, Deeks SG, Ho YC. Filgotinib suppresses HIV-1-driven gene transcription by inhibiting HIV-1 splicing and T cell activation. Journal Of Clinical Investigation 2020, 130: 4969-4984. PMID: 32573496, PMCID: PMC7456222, DOI: 10.1172/jci137371.Peer-Reviewed Original ResearchConceptsHIV-1 reactivationHIV-1-infected cellsT cell activationImmune activationHIV-1-induced immune activationCell activationHIV-1 RNA transcriptionHIV-1-infected individualsDrug screensEffective antiretroviral therapyHIV-1 transcriptionFilgotinib treatmentImmune exhaustionAntiretroviral therapyCell line modelsCancer-related gene expressionHIV-1 splicingViral antigensT cellsDrug treatmentHigh-throughput drug screensJAK inhibitorsFilgotinibDruggable targetsDrug candidates
2021
The Clonal Expansion Dynamics of the HIV-1 Reservoir: Mechanisms of Integration Site-Dependent Proliferation and HIV-1 Persistence
Yeh YJ, Yang K, Razmi A, Ho YC. The Clonal Expansion Dynamics of the HIV-1 Reservoir: Mechanisms of Integration Site-Dependent Proliferation and HIV-1 Persistence. Viruses 2021, 13: 1858. PMID: 34578439, PMCID: PMC8473165, DOI: 10.3390/v13091858.Peer-Reviewed Original ResearchConceptsHIV-1-infected cellsHIV-1 latent reservoirAntiretroviral therapyHIV-1Cancer-related gene expressionHIV-1 promoterHIV-1 integration sitesLatent reservoirClonal expansionClonal expansion dynamicsCancer-related genesLong-term suppressive antiretroviral therapyHIV-1 promoter activitySuppressive antiretroviral therapyLow-level viremiaHIV-1 reservoirHIV-1 persistenceHIV-1 transcriptionCertain cancer-related genesViral reboundGene expressionRare caseLoss of functionTherapeutic agentsTumor suppressor gene
2020
The XPB Subunit of the TFIIH Complex Plays a Critical Role in HIV-1 Transcription, and XPB Inhibition by Spironolactone Prevents HIV-1 Reactivation from Latency
Mori L, Jenike K, Yeh YJ, Lacombe B, Li C, Getzler A, Mediouni S, Cameron M, Pipkin M, Ho YC, Ramirez BC, Valente S. The XPB Subunit of the TFIIH Complex Plays a Critical Role in HIV-1 Transcription, and XPB Inhibition by Spironolactone Prevents HIV-1 Reactivation from Latency. Journal Of Virology 2020, 95: 10.1128/jvi.01247-20. PMID: 33239456, PMCID: PMC7851559, DOI: 10.1128/jvi.01247-20.Peer-Reviewed Original ResearchAntiretroviral therapyHIV-1 transcriptionHIV transcriptionTreatment interruptionCell line modelsViral reservoirAbsence of ARTRapid viral reboundAcute HIV infectionHIV-1 reactivationChronic immune activationHIV-1 latencyLong-term treatmentHIV transcriptional regulationConcentrations of spironolactoneFunctional cure approachesCure approachesCellular mRNA expressionSP treatmentMechanism of actionHIV-1 genomeAldosterone antagonistsViral reboundFunctional cureHIV reactivationRecommendations for measuring HIV reservoir size in cure-directed clinical trials
Abdel-Mohsen M, Richman D, Siliciano RF, Nussenzweig MC, Howell BJ, Martinez-Picado J, Chomont N, Bar KJ, Yu XG, Lichterfeld M, Alcami J, Hazuda D, Bushman F, Siliciano JD, Betts MR, Spivak AM, Planelles V, Hahn BH, Smith DM, Ho YC, Buzon MJ, Gaebler C, Paiardini M, Li Q, Estes JD, Hope TJ, Kostman J, Mounzer K, Caskey M, Fox L, Frank I, Riley JL, Tebas P, Montaner LJ. Recommendations for measuring HIV reservoir size in cure-directed clinical trials. Nature Medicine 2020, 26: 1339-1350. PMID: 32895573, PMCID: PMC7703694, DOI: 10.1038/s41591-020-1022-1.Peer-Reviewed Original ResearchThe forces driving clonal expansion of the HIV-1 latent reservoir
Liu R, Simonetti FR, Ho YC. The forces driving clonal expansion of the HIV-1 latent reservoir. Virology Journal 2020, 17: 4. PMID: 31910871, PMCID: PMC6947923, DOI: 10.1186/s12985-019-1276-8.Peer-Reviewed Original ResearchConceptsHIV-1-infected cellsHIV-1 latent reservoirLatent reservoirAntiretroviral therapyClonal expansionViral reboundHomeostatic proliferationAntigen-specific CD4HIV-1 eradicationHIV-1 replicationT cell functionHIV-1 provirusCertain cancer-related genesCytokine profileAntigen exposureViral loadExhaustion phenotypeLymphoid tissueT cellsClonal expansion dynamicsImmune clearanceCancer-related genesViral expressionCell functionUndetectable levels
2017
Defective HIV-1 Proviruses Are Expressed and Can Be Recognized by Cytotoxic T Lymphocytes, which Shape the Proviral Landscape
Pollack RA, Jones RB, Pertea M, Bruner KM, Martin AR, Thomas AS, Capoferri AA, Beg SA, Huang SH, Karandish S, Hao H, Halper-Stromberg E, Yong PC, Kovacs C, Benko E, Siliciano RF, Ho YC. Defective HIV-1 Proviruses Are Expressed and Can Be Recognized by Cytotoxic T Lymphocytes, which Shape the Proviral Landscape. Cell Host & Microbe 2017, 21: 494-506.e4. PMID: 28407485, PMCID: PMC5433942, DOI: 10.1016/j.chom.2017.03.008.Peer-Reviewed Original ResearchConceptsCytotoxic T lymphocytesHIV-1 provirusT lymphocytesHIV-1-specific cytotoxic T lymphocytesDefective provirusesHIV-1-infected individualsDefective HIV-1 provirusesHIV-1 latency reversalMajor splice donorHIV-1 transcriptsAntiretroviral therapyMemory CD4Latency reversalCTL epitopesHIV-1Proviral landscapeLymphocytesProvirusCellsNovel splice siteAberrant translationCD4Therapy
2013
Replication-Competent Noninduced Proviruses in the Latent Reservoir Increase Barrier to HIV-1 Cure
Ho YC, Shan L, Hosmane NN, Wang J, Laskey SB, Rosenbloom DI, Lai J, Blankson JN, Siliciano JD, Siliciano RF. Replication-Competent Noninduced Proviruses in the Latent Reservoir Increase Barrier to HIV-1 Cure. Cell 2013, 155: 540-551. PMID: 24243014, PMCID: PMC3896327, DOI: 10.1016/j.cell.2013.09.020.Peer-Reviewed Original Research